Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic Syndrome
Conditions
Keywords
Appropriate candidate for transplantation, An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.
Brief summary
The primary objective is to assess the rate of engraftment with combined haploidentical-cord blood transplantation. The secondary objective is to evaluate the incidence and severity of acute and chronic graft-versus-host disease (GVHD).
Interventions
DRUGFludarabine-Melphalan & Rabbit antithymocyte globulin (r-ATG)
Fludarabine is given through the vein daily for 5 days. Melphalan is given through the vein daily for 2 days. ATG is given every day in the vein for four days.
PROCEDUREStem Cell Transplant
Infusion of haploidentical donor, umbilical cord blood
PROCEDUREStem Cells Collections
Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.
DRUGFludarabine, Thiotepa, Antithymocyte globulin (ATG), and Total Body Irradiation (TBI)
Fludarabine is given through the vein daily for 5 days. Thiotepa is given through the vein daily for 2 days. ATG is given through the vein every other day for 4 days. TBI is given twice a day for 3 days.
DRUGFludarabine, Busulfan, and ATG
Fludarabine is given through the vein daily for 5 days. Busulfan is given through the vein daily for 4 days. ATG is given through the vein every other day for 4 days.
Sponsors
University of Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients will be eligible for this study if they have any one of the diseases that are known to be cured after allogeneic stem cell transplantation. 1. Relapsed or refractory acute leukemia (myeloid or lymphoid) 2. Acute leukemia in first remission at high-risk for recurrence 3. Chronic myelogenous leukemia in accelerated phase or blast-crisis 4. Chronic myelogenous leukemia in chronic phase 5. Recurrent or refractory malignant lymphoma or Hodgkin lymphoma 6. Chronic lymphocytic leukemia, relapsed or with poor prognostic features 7. Multiple myeloma 8. Myelodysplastic syndrome 9. Chronic myeloproliferative disease 10. Hemoglobinopathies 11. Aplastic anemia
Exclusion criteria
1. Zubrod performance status \> 2 2. Life expectancy is severely limited by concomitant illness 3. Patients with severely decreased LVEF or impaired pulmonary function tests(PFT's) 4. Estimated Creatinine Clearance \<50 ml/min 5. Serum bilirubin\> 2.0 mg/dl or SGPT \>3 x upper limit of normal 6. Evidence of chronic active hepatitis or cirrhosis 7. HIV-positive 8. Patient is pregnant 9. Patient or guardian not able to sign informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Neutrophil Engraftment | Transplant (Day 0) through Day +28 | Cumulative incidence of graft failure (neutrophil) by day 28 was reported. Patients who did not have neutrophil engraftment before death was considered as a competing risk. Failure to engraft was defined as lack of evidence of hematopoietic recovery (ANC \<500/mm3 and platelet count \< 20,000/mm3) by day +35, confirmed by a biopsy revealing a marrow cellularity \< 5%. Graft failure was also defined as initial myeloid engraftment by day +35, documented to be of donor origin, followed by a drop in the ANC to \< 500/mm3 for more than three days, independent of any myelosuppressive drugs, severe GVHD, CMV, or other infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD) | Up to 2 years | Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). Chronic GVHD is assessed by NIH consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria. (See Citation: Filipovich AH et al) The incidence of patients with acute GVHD (Grade II-IV) was determined at 180 days. The incidence of Chronic GVHD by 2 years was reported |
| Overall Survival- Percentage of Participants Who Survived at 2 Years and 5 Years | up to 5 years | We reported overall survival at 2 years and 5 years after transplant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m\^2 of Fludarabine from Day-7 until Day-3, 140mg/m\^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1. | 87 |
| Total | 87 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Continuous | 45.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 53 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 87 |
| other Total, other adverse events | 0 / 87 |
| serious Total, serious adverse events | 24 / 87 |
Outcome results
Primary
Percentage of Participants With Neutrophil Engraftment
Cumulative incidence of graft failure (neutrophil) by day 28 was reported. Patients who did not have neutrophil engraftment before death was considered as a competing risk. Failure to engraft was defined as lack of evidence of hematopoietic recovery (ANC \<500/mm3 and platelet count \< 20,000/mm3) by day +35, confirmed by a biopsy revealing a marrow cellularity \< 5%. Graft failure was also defined as initial myeloid engraftment by day +35, documented to be of donor origin, followed by a drop in the ANC to \< 500/mm3 for more than three days, independent of any myelosuppressive drugs, severe GVHD, CMV, or other infection.
Time frame: Transplant (Day 0) through Day +28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Percentage of Participants With Neutrophil Engraftment | 85.1 percentage of patients |
Secondary
Overall Survival- Percentage of Participants Who Survived at 2 Years and 5 Years
We reported overall survival at 2 years and 5 years after transplant
Time frame: up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group | Overall Survival- Percentage of Participants Who Survived at 2 Years and 5 Years | Two-year overall survival | 43.7 percentage of patients |
| Treatment Group | Overall Survival- Percentage of Participants Who Survived at 2 Years and 5 Years | Five-year overall survival | 32.9 percentage of patients |
Secondary
Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD)
Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). Chronic GVHD is assessed by NIH consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria. (See Citation: Filipovich AH et al) The incidence of patients with acute GVHD (Grade II-IV) was determined at 180 days. The incidence of Chronic GVHD by 2 years was reported
Time frame: Up to 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group | Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD) | Chronic GVHD | 3.4 percentage of patients |
| Treatment Group | Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD) | Acute GVHD (grade II-IV) | 16.1 percentage of patients |